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Cancer Res. 2003 Aug 1;63(15):4641-7.

Proteomic analysis of intestinal epithelial cells expressing stabilized beta-catenin.

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1
Cancer Proteomics Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Abstract

Aberrant accumulation of beta-catenin protein because of mutation of either the beta-catenin or adenomatous polyposis coli gene plays an essential role in the development of colorectal carcinoma. We established previously a stable clone of the rat small intestinal epithelial cell line IEC6, which is capable of inducing stabilized beta-catenin protein lacking NH(2)-terminal glycogen synthase kinase-3beta phosphorylation site under a strict control of the tetracycline-regulatory system. This clone, IEC6-TetOFF-beta-catenin DeltaN89, shows in vitro polypoid growth on the removal of doxycycline and seems to be an appropriate model for analyzing the molecular mechanisms of early intestinal carcinogenesis. Of >2000 protein spots displayed by newly developed two-dimensional difference gel electrophoresis, 22 were found to be up- or down-regulated on the induction of stabilized beta-catenin. The majority of these proteins fell into two categories: (a) redox-status regulatory proteins and (b) cytoskeleton-associated proteins. Representatively, a key redox-status regulatory protein, manganese superoxide dismutase, up-regulated in IEC6 cells expressing stabilized beta-catenin protein, was overexpressed in adenoma and adenocarcinoma cells of familial adenomatous polyposis patients in parallel with the accumulation of beta-catenin. These results suggest that aberrant accumulation of beta-catenin might contribute to colorectal carcinogenesis by affecting redox status in the mitochondria of intestinal epithelial cells.

PMID:
12907644
[Indexed for MEDLINE]
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